mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for HCN4
Gene summary
Basic gene Info.Gene symbolHCN4
Gene namehyperpolarization activated cyclic nucleotide-gated potassium channel 4
SynonymsSSS2
CytomapUCSC genome browser: 15q24.1
Type of geneprotein-coding
RefGenesNM_005477.2,
Descriptionhyperpolarization activated cyclic nucleotide-gated cation channel 4potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Modification date20141219
dbXrefs MIM : 605206
HGNC : HGNC
Ensembl : ENSG00000138622
HPRD : 09240
Vega : OTTHUMG00000137563
ProteinUniProt: Q9Y3Q4
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_HCN4
BioGPS: 10021
PathwayNCI Pathway Interaction Database: HCN4
KEGG: HCN4
REACTOME: HCN4
Pathway Commons: HCN4
ContextiHOP: HCN4
ligand binding site mutation search in PubMed: HCN4
UCL Cancer Institute: HCN4
Assigned class in mutLBSgeneDBA: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for HCN4.1. "Xu X, Marni F, Wu S, Su Z, Musayev F, Shrestha S, Xie C, Gao W, Liu Q, Zhou L. Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. Structure. 2012 Dec 5;20(12):2116-23. doi: 10.1016/j.str.2012.09.017. Epub 2012 Oct 25. PubMed PMID: 23103389." 23103389

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0071320cellular response to cAMP16407510
GO:0071321cellular response to cGMP22748890
GO:0071805potassium ion transmembrane transport16407510


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Ligand binding site mutations for HCN4
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
 
: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
L708A707GBLCA1
R669R669HCOAD1
R669R668QCOAD1
F613E614QLUAD1
F613R612HLUAD1
R713R713HLUAD1
R713D712ELUAD1
F564,E566D565VSTAD1
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.


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Protein structure related information for HCN4
Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
F613R612H-1.4972034
F613E614Q-1.3270697
R713R713H-1.3267193
R669R668Q-1.2690316
L708A707G-0.87430219
R669R669H-0.49379184
F564D565V-0.32419279
E566D565V-0.32419279
R713D712E-0.30537518
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for HCN4 from PDB

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Differential gene expression and gene-gene network for HCN4
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of HCN4 and the right PPI network was created from samples without mutations in the LBS of HCN4. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for HCN4
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C1834144Sick Sinus Syndrome 2, Autosomal Dominant2Biomarker, GeneticVariation
umls:C0004238Atrial Fibrillation1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for HCN4
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of HCN4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
PCGCYCLIC GMP4kl1AF564 E566 F613
PCGCYCLIC GMP4kl1BF564 E566 F613
PCGCYCLIC GMP4kl1CF564 E566 F613
PCGCYCLIC GMP4kl1DF564 E566 F613
CMP3',5'-CYCLIC AMP3otfAR669
CMP3',5'-CYCLIC AMP3u11BR669
7CH7-CH-CAMP(2S,4AR,6R,7R,7AS)-6-(4-AMINO-7H-PYRROLO[2,3- D]PYRIMIDIN-7-YL)TETRAHYDRO-4H-FURO[3,2-D][1,3, 2]DIOXAPHOSPHININE-2,7-DIOL 2-OXIDE4nvpAR669
PCGCYCLIC GMP4kl1AR669
PCGCYCLIC GMP4kl1CR669
CMP3',5'-CYCLIC AMP3u11AR669 R713
CMP3',5'-CYCLIC AMP4hbnAR669 R713
PCGCYCLIC GMP4kl1BR669 R713
PCGCYCLIC GMP4kl1DR669 R713


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Conservation information for LBS of HCN4
Multiple alignments for Q9Y3Q4 in multiple species
LBSAA sequence# speciesSpecies


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